The aim of this paper is to investigate the protective effect of curcumin on zearalenone-induced liver injury in piglets and to explore its molecular mechanism to provide a theoretical basis for the alleviation of ZEN-induced liver injury in piglets by nutritional means in production. Twenty-four female weaned piglets (Duroc×Long White×Large White, 7.43±0.88 kg) were randomly divided into three groups: control (CON), ZEN (2 mg/kg), and ZEN+CUR (2 mg/kg ZEN + 300 mg/kg CUR). The trial lasted 28 days following a 3-day pre-feeding period. The results showed that ZEN significantly reduced piglets' body weight on day 28 compared to the CON group, but CUR supplementation restored body weight. ZEN also decreased average daily gain (ADG) and feed intake (ADFI), while CUR improved these parameters in the ZEN+CUR group. ZEN increased the liver index, causing hepatomegaly, but CUR treatment reduced the liver index. Histologically, ZEN caused liver cell swelling, hemorrhage, and vacuolar degeneration, while CUR improved these pathological changes. Serum analysis revealed that ZEN increased alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bile acids (TBA), total bilirubin (TBIL), and γ-glutamyltransferase (GGT) levels, but CUR effectively restored these levels. ZEN had no significant effect on serum aspartate aminotransferase (AST) or albumin (ALB) levels. Overall, CUR demonstrated a protective effect against ZEN-induced liver injury in piglets.